Ying Chen

Yuxiang Lin, Ling Luo, Ying Chen et al.

Spatial transcriptomics (ST) provides high-resolution pathological images and whole-transcriptomic expression profiles at individual spots across whole-slide scales. This setting makes it an ideal data source to develop multimodal foundation models. Although recent studies attempted to fine-tune visual encoders with trainable gene encoders based on spot-level, the absence of a wider slide perspective and spatial intrinsic relationships limits their ability to capture ST-specific insights effectively. Here, we introduce ST-Align, the first foundation model designed for ST that deeply aligns image-gene pairs by incorporating spatial context, effectively bridging pathological imaging with genomic features. We design a novel pretraining framework with a three-target alignment strategy for ST-Align, enabling (1) multi-scale alignment across image-gene pairs, capturing both spot- and niche-level contexts for a comprehensive perspective, and (2) cross-level alignment of multimodal insights, connecting localized cellular characteristics and broader tissue architecture. Additionally, ST-Align employs specialized encoders tailored to distinct ST contexts, followed by an Attention-Based Fusion Network (ABFN) for enhanced multimodal fusion, effectively merging domain-shared knowledge with ST-specific insights from both pathological and genomic data. We pre-trained ST-Align on 1.3 million spot-niche pairs and evaluated its performance through two downstream tasks across six datasets, demonstrating superior zero-shot and few-shot capabilities. ST-Align highlights the potential for reducing the cost of ST and providing valuable insights into the distinction of critical compositions within human tissue.

Haicheng Wang, Chen Ju, Weixiong Lin et al.

In rapidly evolving field of vision-language models (VLMs), contrastive language-image pre-training (CLIP) has made significant strides, becoming foundation for various downstream tasks. However, relying on one-to-one (image, text) contrastive paradigm to learn alignment from large-scale messy web data, CLIP faces a serious myopic dilemma, resulting in biases towards monotonous short texts and shallow visual expressivity. To overcome these issues, this paper advances CLIP into one novel holistic paradigm, by updating both diverse data and alignment optimization. To obtain colorful data with low cost, we use image-to-text captioning to generate multi-texts for each image, from multiple perspectives, granularities, and hierarchies. Two gadgets are proposed to encourage textual diversity. To match such (image, multi-texts) pairs, we modify the CLIP image encoder into multi-branch, and propose multi-to-multi contrastive optimization for image-text part-to-part matching. As a result, diverse visual embeddings are learned for each image, bringing good interpretability and generalization. Extensive experiments and ablations across over ten benchmarks indicate that our holistic CLIP significantly outperforms existing myopic CLIP, including image-text retrieval, open-vocabulary classification, and dense visual tasks.